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Pharmacokinetics of rifampicin in adult TB patients and healthy volunteers: a systematic review and meta-analysis
OBJECTIVES: The objectives of this study were to explore inter-study heterogeneity in the pharmacokinetics (PK) of orally administered rifampicin, to derive summary estimates of rifampicin PK parameters at standard dosages and to compare these with summary estimates for higher dosages. METHODS: A sy...
Autores principales: | , , , , , , , , , , , , , , |
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Formato: | Online Artículo Texto |
Lenguaje: | English |
Publicado: |
Oxford University Press
2018
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Materias: | |
Acceso en línea: | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6105874/ https://www.ncbi.nlm.nih.gov/pubmed/29701775 http://dx.doi.org/10.1093/jac/dky152 |
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author | Stott, K E Pertinez, H Sturkenboom, M G G Boeree, M J Aarnoutse, R Ramachandran, G Requena-Méndez, A Peloquin, C Koegelenberg, C F N Alffenaar, J W C Ruslami, R Tostmann, A Swaminathan, S McIlleron, H Davies, G |
author_facet | Stott, K E Pertinez, H Sturkenboom, M G G Boeree, M J Aarnoutse, R Ramachandran, G Requena-Méndez, A Peloquin, C Koegelenberg, C F N Alffenaar, J W C Ruslami, R Tostmann, A Swaminathan, S McIlleron, H Davies, G |
author_sort | Stott, K E |
collection | PubMed |
description | OBJECTIVES: The objectives of this study were to explore inter-study heterogeneity in the pharmacokinetics (PK) of orally administered rifampicin, to derive summary estimates of rifampicin PK parameters at standard dosages and to compare these with summary estimates for higher dosages. METHODS: A systematic search was performed for studies of rifampicin PK published in the English language up to May 2017. Data describing the C(max) and AUC were extracted. Meta-analysis provided summary estimates for PK parameter estimates at standard rifampicin dosages. Heterogeneity was assessed by estimation of the I(2) statistic and visual inspection of forest plots. Summary AUC estimates at standard and higher dosages were compared graphically and contextualized using preclinical pharmacodynamic (PD) data. RESULTS: Substantial heterogeneity in PK parameters was evident and upheld in meta-regression. Treatment duration had a significant impact on the summary estimates for rifampicin PK parameters, with C(max) 8.98 mg/L (SEM 2.19) after a single dose and 5.79 mg/L (SEM 2.14) at steady-state dosing, and AUC 72.56 mg·h/L (SEM 2.60) and 38.73 mg·h/L (SEM 4.33) after single and steady-state dosing, respectively. Rifampicin dosages of at least 25 mg/kg are required to achieve plasma PK/PD targets defined in preclinical studies. CONCLUSIONS: Vast inter-study heterogeneity exists in rifampicin PK parameter estimates. This is not explained by the available modifying variables. The recommended dosage of rifampicin should be increased to improve efficacy. This study provides an important point of reference for understanding rifampicin PK at standard dosages as efforts to explore higher dosing strategies continue in this field. |
format | Online Article Text |
id | pubmed-6105874 |
institution | National Center for Biotechnology Information |
language | English |
publishDate | 2018 |
publisher | Oxford University Press |
record_format | MEDLINE/PubMed |
spelling | pubmed-61058742018-08-27 Pharmacokinetics of rifampicin in adult TB patients and healthy volunteers: a systematic review and meta-analysis Stott, K E Pertinez, H Sturkenboom, M G G Boeree, M J Aarnoutse, R Ramachandran, G Requena-Méndez, A Peloquin, C Koegelenberg, C F N Alffenaar, J W C Ruslami, R Tostmann, A Swaminathan, S McIlleron, H Davies, G J Antimicrob Chemother Systematic Review OBJECTIVES: The objectives of this study were to explore inter-study heterogeneity in the pharmacokinetics (PK) of orally administered rifampicin, to derive summary estimates of rifampicin PK parameters at standard dosages and to compare these with summary estimates for higher dosages. METHODS: A systematic search was performed for studies of rifampicin PK published in the English language up to May 2017. Data describing the C(max) and AUC were extracted. Meta-analysis provided summary estimates for PK parameter estimates at standard rifampicin dosages. Heterogeneity was assessed by estimation of the I(2) statistic and visual inspection of forest plots. Summary AUC estimates at standard and higher dosages were compared graphically and contextualized using preclinical pharmacodynamic (PD) data. RESULTS: Substantial heterogeneity in PK parameters was evident and upheld in meta-regression. Treatment duration had a significant impact on the summary estimates for rifampicin PK parameters, with C(max) 8.98 mg/L (SEM 2.19) after a single dose and 5.79 mg/L (SEM 2.14) at steady-state dosing, and AUC 72.56 mg·h/L (SEM 2.60) and 38.73 mg·h/L (SEM 4.33) after single and steady-state dosing, respectively. Rifampicin dosages of at least 25 mg/kg are required to achieve plasma PK/PD targets defined in preclinical studies. CONCLUSIONS: Vast inter-study heterogeneity exists in rifampicin PK parameter estimates. This is not explained by the available modifying variables. The recommended dosage of rifampicin should be increased to improve efficacy. This study provides an important point of reference for understanding rifampicin PK at standard dosages as efforts to explore higher dosing strategies continue in this field. Oxford University Press 2018-09 2018-04-26 /pmc/articles/PMC6105874/ /pubmed/29701775 http://dx.doi.org/10.1093/jac/dky152 Text en © The Author(s) 2018. Published by Oxford University Press on behalf of the British Society for Antimicrobial Chemotherapy. http://creativecommons.org/licenses/by/4.0/ This is an Open Access article distributed under the terms of the Creative Commons Attribution License (http://creativecommons.org/licenses/by/4.0/), which permits unrestricted reuse, distribution, and reproduction in any medium, provided the original work is properly cited. |
spellingShingle | Systematic Review Stott, K E Pertinez, H Sturkenboom, M G G Boeree, M J Aarnoutse, R Ramachandran, G Requena-Méndez, A Peloquin, C Koegelenberg, C F N Alffenaar, J W C Ruslami, R Tostmann, A Swaminathan, S McIlleron, H Davies, G Pharmacokinetics of rifampicin in adult TB patients and healthy volunteers: a systematic review and meta-analysis |
title | Pharmacokinetics of rifampicin in adult TB patients and healthy volunteers: a systematic review and meta-analysis |
title_full | Pharmacokinetics of rifampicin in adult TB patients and healthy volunteers: a systematic review and meta-analysis |
title_fullStr | Pharmacokinetics of rifampicin in adult TB patients and healthy volunteers: a systematic review and meta-analysis |
title_full_unstemmed | Pharmacokinetics of rifampicin in adult TB patients and healthy volunteers: a systematic review and meta-analysis |
title_short | Pharmacokinetics of rifampicin in adult TB patients and healthy volunteers: a systematic review and meta-analysis |
title_sort | pharmacokinetics of rifampicin in adult tb patients and healthy volunteers: a systematic review and meta-analysis |
topic | Systematic Review |
url | https://www.ncbi.nlm.nih.gov/pmc/articles/PMC6105874/ https://www.ncbi.nlm.nih.gov/pubmed/29701775 http://dx.doi.org/10.1093/jac/dky152 |
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